Tolerance to self and foreign antigens is an active process that is mediated by multiple mechanisms. Central tolerance is promoted by negative selection or central deletion of a large number of lymphocytes capable of reacting to self molecules. However, some self-reactive lymphocytes escape this process and remain present in the adult and must be regulated by active tolerance mechanisms that involve T regulatory cells, anergy, or apoptosis. Here, we will study a model for peripheral tolerance that can be induced through the eye called Anterior Chamber Associated Immune Deviation (ACAID). The eye is an immune privileged site that has evolved to exhibit immunosuppressive mechanisms that prevent immune inflammatory reactions in the eye in order to preserve vision. In order to better understand how we might adapt ACAID mechanism to immunotherapy of autoimmune disease in the eye, our first aim will investigate the mechanisms of ACAID induction in sensitized vs na[unreadable]ve mice. During these studies we will also induce antigen specific ACAID in mice that receive cornea transplants or in which experimental autoimmune uveitis is induced by transferring in vitro generated ACAID- like tolerogenic APC, and explore the role of the NKT cell in this therapy. The results of these studies will raise the possibility of a cell based therapy to treat immune inflammatory diseases in the eye.